Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer G46B Bronx, 10461 NY, USA.
Cardiovasc Res. 2017 Oct 1;113(12):1453-1464. doi: 10.1093/cvr/cvx146.
Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling.
右心室衰竭可预测肺动脉高压 (PH) 患者的不良预后，并且与左心室心力衰竭患者相关，并与间质纤维化有关。这篇综述文章讨论了涉及右心室纤维化的细胞效应物和分子机制。右心室间质包含血管细胞、成纤维细胞和免疫细胞，嵌入在基于胶原蛋白的基质中。PH 中的右心室压力超负荷与成纤维细胞群体的扩张、肌成纤维细胞的激活以及细胞外基质蛋白的分泌有关。肾上腺素能信号的机械敏感性转导和肾素-血管紧张素-醛固酮级联的刺激触发右心室成纤维细胞的激活。炎性细胞因子和趋化因子可能有助于巨噬细胞的扩张和激活，巨噬细胞可能作为成纤维生长因子（如转化生长因子 (TGF)-β）的来源。内皮素-1、TGF-βs 和基质细胞蛋白协同作用激活心肌成纤维细胞，并促进基质蛋白的合成。与左心室相比，RV 很好地耐受容量超负荷和缺血；RV 间质细胞和基质是否参与这些有利反应尚不清楚。成纤维细胞的扩张和细胞外基质蛋白的沉积是致心律失常性右心室心肌病的突出特征，可能与心律失常事件的发病机制有关。关于右心室重塑的流行概念范式是基于对左心室损伤模型中发现的推断。考虑到 RV 的独特胚胎学、形态学和生理学特性以及右心室衰竭的临床意义，需要进一步剖析 RV 特有的纤维化和间质重塑机制。
